Neurogenesis in drosophila

L14

In what conditions is the neurogenic region set up in drosophila?

ventrolaterally at a low level of nuclear Dorsal protein through rhomboid expression

Why is neurogenesis studied in drosophila?

analogous with vertebrate neurogenesis

Through what mechanism does the mesoderm form internal structures? How does this affect the neuroectoderm?

invaginates

neuroectoderm brought together and lies ventrally - giving rise to neurons

Where does the neural tube develop in vertebrates? How does this compare to drosophila?

dorsal side

in drosophila neurons rise ventrally

What explains the inversion noticed where structures form in opposite axes in drosophila vs humans?

same signalling pathway Dpp/BMP = ventral vs dorsal patterning in each

Where does the circulatory system develop in flies vs humans?

dorsal // ventral

At what evolutionary stage did the inversion between flies and humans happen?

in the lineage leading to the chordates/vertebrates, after the echinoderms split off within deuterostomes

How do neural plate genes compare in drosophila vs mice (deuterostomes)?

homologous genes, just reverse the circular drosophila gene complex to correspond to gene order left to right

Which pathway is important to set up the neural region axis?

Dpp/BMP

What process does lateral inhibition describe?

certain cells in the neuroectoderm will be selected to become neurons, others will stay ectoderm

What is a proneural cluster?

~ equivalent cells within the neuroectoderm any of which can give rise to a neuron, but only one does

Describe neurogenesis

development of nervous tissue

Which genes set up the proneural cluster?

proneural genes Achaete and Scute

Which signalling pathway triggers and ensures lateral inhibition and essentially neurogenesis?

Notch/Delta pathway

Is Notch/Delta cell-cell or transcription factor?

cell-cell

Which proteins activate the Delta/Notch signalling pathway? What does this cause?

Achaete-Scute proteins

selection of a single cell to give rise to a neuron within a proneural cluster

What do Achaete Scute proteins promote the expression of?

delta transmembrane ligand

What cells can Delta influence? Why?

direct neighbouring cells bc is a transmembrane ligand so stuck in cell membrane

Is delta expression the same between all neighbouring cells within a proneural cluster?

No cell is really EXACTLY the same = small differences in the level of delta that a cell expresses

How does a strong signal affect Achaete/Scute expression? What effect does this have?

downregulate

small difference in Achaete Scute will become amplified, so more expressed in a cell with less Notch

What activates neural genes?

High and continuous achaete/scute expression ie low Notch signal

What is the fate of a “losing“ cell within a proneuronal cluster? (ie doesn’t give rise to a neuron)

”losing cell” reverts to epidermal fate

How many proneural clusters are there per segment?

8

What is vsx1?

marker for a particular type of interneuron

In a proneural cluster, what would Notch deficiency cause?

no notch = no inhibition of achaete/scute = their continuous activity leads to activated neural genes = all cells give rise to neuroblasts - no epidermal cells

In a proneural cluster, what would Notch hyperactivity cause?

lots of notch = lots of achaete/scute inhibition = no activity leads to the cells remaining epidermal cells ie no neuroblasts

What do neuroblasts, selected through lateral inhibition, give rise to?

either neuronal or glial cells

What process leads to the generation of a neuron or glia from a neuroblast?

asymmetric cell division

In what types of organisms do asymmetric cell division and lateral inhibition occur?

various tissues, mammals, drosophila etc - basic developmental principle

What physically happens to the neuroblast after its win in lateral inhibition?

drops down from the epithelium into the interior of the embryo

What type of memory do epidermis cells have in drosophila? And neuroblasts?

apico-basal polarity - inherent polarity

they remember the apico basal polarity they had as an epidermal cell

What allows the memory that neuroblasts keep throughout their development?

localised protein complexes like:

• Apical: Bazooka (Par 3 in mammals), Inscuteable (Insc)/Pins

• Basal: Numb

What is Numb’s role?

basal side of the neural cell directing proteins and RNAs + orients the mitotic spindle = plane of division

What does asymmetric cell division describe?

• neuroblast: stem cell that can undergo further asymmetric divisions

• ganglion mother cell: divides once more and gives rise to a neuron or glia

What are the steps of the stereotypic manner in which neuronal and glial cells are generated?

• delamination of embryonic neuroblast - cell migrates

• localisation of determinants - drop to interior of the embryo

• orientation of the mitotic spindle = plane of division

• asymmetric cell division into either neuroblast or ganglion mother cell

What’s an imaginal disc?

precursor tissues that develop into adult body parts like wings, legs, and the head during metamorphosis

What other specification processes are similar to the development of neuronal and glial cells?

process used to specify adult sensory neurons

What are the different fates of cells in precursor sensory organs?

socket, bristle, sheath or sensory neuron cells

How is the embryonic cerebral cortex also dependent on asymmetric cell division?

proper development depends on glial and neural cells being made so proper division is necessary with:

• stem cells: high mPar3 during interphase - disperses during m phase

• glial progenitors - more par3 so more notch

• neuronal or interneuron precursors less par3 so less notch

Define an arthropod

invertebrates in the phylum Arthropoda with differentiated segments like drosophila

What is a mitotic spindle?

structure within eukaryotic cells responsible for separating duplicated chromosomes during cell division

What are 2 important genes involved in neuroblast specification?

bazooka and insc/pins + numb