cell biology, diversity and development

What are the basic compartments of a eukaryotic cell?

nucleus (DNA storage and transcription)

mitochondria (ATP production)

endoplasmic reticulum (protein and lipid synthesis)

Golgi apparatus (protein modification and packaging)

plasma membrane (selective barrier)

cytoskeleton (structural support)

lysosomes (waste breakdown)

What is the function of the nucleus in a eukaryotic cell?

The nucleus contains DNA, is the site of transcription, and has the nucleolus for ribosome assembly.

Describe the structure and function of mitochondria.

Mitochondria have a double membrane with cristae, produce ATP through oxidative phosphorylation, contain mitochondrial DNA (mtDNA), and are essential for energy production.

What are the differences between rough and smooth endoplasmic reticulum?

Rough ER has ribosomes and is involved in protein synthesis; smooth ER lacks ribosomes and is involved in lipid synthesis and detoxification.

What is the role of the Golgi apparatus?

The Golgi apparatus modifies, sorts, and packages proteins received from the ER into vesicles for transport.

What is the plasma membrane composed of, and what is its function?

The plasma membrane is a phospholipid bilayer with embedded proteins, acting as a selective barrier to regulate the entry and exit of substances.

What is the cytoskeleton, and what are its components?

The cytoskeleton is a network of proteins (microfilaments, microtubules, intermediate filaments) providing structural support, aiding in cell movement, and facilitating division.

What are lysosomes, and what do they do?

Lysosomes contain enzymes for breaking down waste materials and cellular debris, maintaining cellular homeostasis.

What are the four main compartments of a neuron, and what are their functions?

Dendrites: receive synaptic inputs

Cell body (soma): metabolic center

Axon: transmits action potential

Axon terminal: releases neurotransmitters.

What is the role of dendrites in a neuron?

Dendrites receive synaptic inputs from other neurons and sum these signals to potentially trigger an action potential at the axon initial segment (AIS).

What is the function of the cell body (soma) in a neuron?

The cell body is the metabolic center, containing organelles like the nucleus, ER, Golgi, and mitochondria, and is responsible for maintaining the neuron's integrity and function.

Describe the structure and function of the axon.

The axon is a long projection that conducts action potentials away from the cell body. It can be myelinated to increase conduction speed.

What are the presynaptic terminals, and what happens there?

Presynaptic terminals are the ends of axons where neurotransmitters are released into the synaptic cleft to transmit signals to the postsynaptic cell.

What is myelination, and why is it important?

Myelination is the process where axons are insulated with a lipid-rich layer (myelin) to increase the speed of action potential conduction. It is provided by Schwann cells in the PNS and oligodendrocytes in the CNS.

What are nodes of Ranvier, and what is their function?

Nodes of Ranvier are gaps in the myelin sheath where action potentials are regenerated, allowing for saltatory conduction, which speeds up signal transmission.

What is the synaptic cleft, and what occurs there?

The synaptic cleft is the narrow space between the presynaptic and postsynaptic cells where neurotransmitters are released and bind to receptors on the postsynaptic cell.

What is the structure of DNA?

DNA is a double-stranded helix with a sugar-phosphate backbone and base pairs A-T, C-G.

What are histones, and how do they affect gene expression?

Histones are proteins around which DNA is wrapped. Tight wrapping (heterochromatin) reduces transcription, while loose wrapping (euchromatin) increases transcription.

What is the central dogma of molecular biology?

The central dogma is DNA → RNA → Protein, where DNA is transcribed into mRNA, which is then translated into proteins.

Describe the process of transcription.

Transcription involves initiation (RNA polymerase binds to promoter), elongation (synthesis of mRNA), and termination (release of mRNA).

What is splicing, and why is it important?

Splicing is the removal of introns and joining of exons in pre-mRNA to form mature mRNA. Alternative splicing allows for different protein isoforms from the same gene.

What is a codon, and what is its role in protein synthesis?

A codon is a sequence of three nucleotides in mRNA that codes for a specific amino acid. The genetic code consists of 64 codons, including start (AUG) and stop codons.

Describe the process of translation.

Translation occurs in ribosomes and involves initiation (start codon AUG), elongation (adding amino acids), and termination (stop codon).

What is the difference between rough and smooth endoplasmic reticulum in terms of function?

Rough ER is involved in protein synthesis (has ribosomes), while smooth ER is involved in lipid synthesis and detoxification (no ribosomes).

What happens to proteins after they are synthesized in the rough ER?

Proteins are transported to the Golgi apparatus for modification and packaging.

What is the role of the Golgi apparatus in protein processing?

The Golgi apparatus modifies proteins (post-translational modification), sorts them, and packages them into vesicles for transport.

Why are mitochondria important for cellular function?

Mitochondria produce ATP, the cell's energy currency, through oxidative phosphorylation, essential for many cellular processes.

What are the four main types of macromolecules, and what are their functions?

Carbohydrates (energy storage, structural roles), Proteins (enzymes, structural components, etc.), Nucleic acids (store and transfer genetic information), Lipids (membrane structure, energy storage).

How are neurons specialized compared to other eukaryotic cells?

Neurons are specialized for signal transmission with structures like dendrites, axons, and synapses, and have high metabolic demands supported by organelles like mitochondria.

What is the start codon in mRNA, and what amino acid does it code for?

The start codon is AUG, which codes for methionine.

What are the three stop codons in mRNA?

UAA, UAG, UGA.

What is the function of the nucleolus?

The nucleolus is where ribosomal RNA is synthesized and ribosomes are assembled.

What are the two types of endoplasmic reticulum, and how can you distinguish them?

Rough ER has ribosomes attached, involved in protein synthesis; smooth ER does not have ribosomes, involved in lipid synthesis.

What is the difference between transcription and translation?

Transcription is the synthesis of mRNA from DNA, while translation is the synthesis of proteins from mRNA.

Where does transcription occur in eukaryotic cells?

Transcription occurs in the nucleus.

Where does translation occur in eukaryotic cells?

Translation occurs in the cytoplasm, on ribosomes.

What is the role of tRNA in translation?

tRNA brings specific amino acids to the ribosome during translation, matching the codons on mRNA with the appropriate amino acids.

What is the function of the spliceosome?

The spliceosome is a complex that removes introns from pre-mRNA during splicing.

What is alternative splicing, and why is it important?

Alternative splicing allows different combinations of exons to be included in the mature mRNA, leading to different protein isoforms from the same gene, increasing protein diversity.

What are neurotransmitters, and how do they function in synaptic transmission?

Neurotransmitters are chemicals released from the presynaptic terminal into the synaptic cleft, where they bind to receptors on the postsynaptic cell to transmit signals.

What is the difference between excitatory and inhibitory neurotransmitters?

Excitatory neurotransmitters increase the likelihood of an action potential in the postsynaptic cell, while inhibitory neurotransmitters decrease it.

What are the three main types of neurons based on function?

Sensory neurons (afferent), motor neurons (efferent), and interneurons.

What is the approximate number of neurons in the human brain?

86 billion

What is the approximate number of glial cells in the human brain?

85 billion

What are the basic structural components of all neurons?

Dendrites, cell body (soma), axon, presynaptic terminals

Why is neuronal diversity important for brain functions?

It allows the brain to perform a wide range of cognitive, sensory, and motor functions

What are the four main features used to define neuronal cell types?

Morphology, location, function, gene expression

How does morphology help in defining a neuronal cell type?

The shape of dendritic and axonal trees reveals the neuron's role in neural circuits

What role does location play in defining neuronal cell types?

Different brain regions have specialized neurons, and cortical layers have specific projection patterns

How does function contribute to defining neuronal cell types?

Through neurotransmitters released and electrophysiological firing patterns

What is the significance of gene expression in defining neuronal cell types?

It provides a molecular profile that reflects the cell's type, function, and state

What is a key morphological feature of Purkinje cells, and why is it important?

Large dendritic trees, allowing them to process complex inputs for fine motor control

Who developed the Golgi staining technique, and when?

Santiago Ramón y Cajal in the late 1880s

What modern technique is used to reconstruct axonal arbors?

Viral labeling

What are retinal ganglion cells specialized for?

Light detection

What type of neurons are found in cortical layers 2/3, and where do they project?

Callosal Projection Neurons (CPN), project to other cortical areas

What type of neurons are found in cortical layers 5/6, and where do they project?

Neurons that project to subcortical areas (e.g., brainstem, spinal cord, thalamus)

How are inhibitory interneurons distributed in the cortex?

Present across all layers, but their laminar positions are less defined than excitatory neurons

What is the primary excitatory neurotransmitter in the cortex?

Glutamate

What is the primary inhibitory neurotransmitter in the cortex?

GABA

How do basket cells and Deep Martinotti cells differ in their electrophysiological properties?

Basket cells fire at higher frequencies than Deep Martinotti cells, indicating different inhibitory roles

What is the transcriptome?

The total set of mRNA transcripts in a cell, reflecting its gene expression profile

What is single-cell RNA sequencing, and how is it used to study's neuronal cell types?

A technique to analyze gene expression in individual cells, grouping neurons by similar transcriptomes to classify cell types

What is the primary cause of epilepsy in terms of neuronal function?

Dysregulation of the excitatory-inhibitory balance, leading to seizures

Which specific neurons are affected in Parkinson's disease, and where are they located?

Dopaminergic neurons in the substantia nigra

Why are mouse models used to study neuronal cell types?

Many neuronal types are conserved between mice and humans, allowing for research on similar cell types

What is a human-specific neuronal cell type not found in mice?

Rosehip neuron, a specialized inhibitory interneuron in the human cortex

What is the estimated number of inhibitory neuron subtypes based on gene expression?

23 subtypes

What is connectomics, and what are its challenges?

Connectomics is the study of neural connections to create a brain "wiring diagram"; it is expensive and time-consuming

What is neurulation?

Neurulation is the process by which the neural tube forms from the ectoderm in early embryonic development.

What are the three derm layers in early embryogenesis?

Ectoderm, mesoderm, and endoderm.

Which germ layer gives rise to the nervous system?

Ectoderm.

Describe the steps of neurulation.

The neural plate forms from the ectoderm,

buckles to form the neural groove,

and the dorsal neural folds fuse to form the neural tube.

What does the rostral region of the neural tube become?

The brain.

What does the caudal region of the neural tube become?

The spinal cord.

What are neuroepithelial cells?

Founder cells of the nervous system that divide symmetrically to self-renew and expand.

What is the role of radial glia in neurogenesis?

Radial glia generate all neurons of the brain through symmetric and asymmetric divisions.

What is direct neurogenesis?

Asymmetric division of radial glia producing one radial glia and one neuron.

What is indirect neurogenesis?

Asymmetric division of radial glia producing one radial glia and one intermediate progenitor, which then divides to produce two neurons.

When does neurogenesis begin in human cortical development?

Around 6 weeks post-conception.

What is the process by which newly made neurons reach their correct position in the cortex?

Radial migration.

In which trimester do deep layer cortical neurons form?

Second trimester.

In which order are cortical layers generated?

Inside-out manner, with deep layers (e.g., layer 6) forming first, followed by upper layers.

Where are inhibitory interneurons generated, and how do they reach the cortex?

Generated in the ganglionic eminences (ventral forebrain) and migrate tangentially to the cortex.

What happens to radial glia by the end of neurogenesis?

They differentiate into astrocytes.

What type of cortex do humans have, and what does it allow?

Gyrencephalic cortex, which allows for greater expansion of cell number and higher cognitive functions.

What type of cortex do mice have?

Lissencephalic cortex.

Do mice have outer radial glia?

No, unlike humans.

How do the number of neurons in human and mouse brains compare?

Humans have approximately 16.3 billion neurons, while mice have about 13.7 million.

What are human induced pluripotent stem cells (iPSCs)?

Stem cells reprogrammed to an unspecialized state, capable of differentiating into any cell type.

What can iPSCs be differentiated into for studying brain development?

2D neurons or 3D organoids.

What is the difference between undirected and directed differentiation in organoids?

Undirected models general brain development, while directed targets specific brain regions using specific factors.

How can organoids help study microcephaly?

By modeling both environmental (e.g., Zika virus) and genetic (e.g., CDK5RAP2 mutations) causes of microcephaly.

What are assembloids, and what can they model?

Assembloids are combinations of organoids that can model complex pathways, such as the cortico-spinal-muscle pathway.

What happens to radial glia around 12 weeks post-conception?

They become outer radial glia in the subventricular zone.

Does tangential migration of cortical interneurons continue after birth in humans?

Yes, it continues postnatally.

How does the Zika virus cause microcephaly in organoid models?

It targets neural progenitor cells, reducing neurogenesis.

What is the effect of the CDK5RAP2 mutation in microcephaly?

It causes early differentiation of neural progenitor cells into neurons, reducing the progenitor pool and leading to a smaller brain.

What does "glia" mean and why were glial cells historically overlooked?

"Glia" comes from the Greek word for glue; glial cells were once thought to only support neurons, not contribute to brain function.

When did the physiological study of glia begin?

In the 1950s.