Unit 3 - Molecules to Cells

Critical Period for CNS

Week 3-16 of Fertilization

Critical Period for Heart

Week 3-6 of Fertilization (still at risk til 8)

Juxtacrine

Contact dependent signaling / proteins are passed from cell to cell

Fibroblast Growth Factors (FGF)

-blood vessel growth -axon growth -injury repair -mesoderm differentiation

Fibroblast

Connective tissue cell, secrete collagen and extracellular matrix

WNT proteins

-limb patterning -bone differentiation -midbrain development -somite differentiation -elongation of body systems (neural tube) -tissue homeostasis, regeneration, and healing

TGF Superfamily

-tissue differentiation -front to back (dorsoventral) patterning -bone, connective, and epithelial tissue formation (lungs, kidney, CNS)

SHH

-Left-right Axis formation -midline structures -controls GLI family of TFs

HOX genes

-”master control” -homeobox genes -TFs that control other genes -ultimately determine body patterning through regulation -determine the ID of segments or structures of body

Primary Ciliary Dyskinesia

-primary cilia do not move properly

-leads to lack of cell signal gradient

-cause of abn. L/R patterning (heterotaxy)

-mostly AR

Major birth defect

-afrects health or fxn or significantly affects form (ex: heart defects, missing limbs, clefts)

Dysplasia

-intrinsic issue with tissue formation

-never “normal”

Disruption / Deformation

-Formed / previously normal structure(s) acted upon by force

-ex: amniotic bands (disruption) or oligohydramnios (Deformation)

Potter Facies

-Vert low AF levels → small uterine vol and lack of space for fetus → compressed face and limb deform.

-Lack of lung development due to lack of fluid

Syndrome

-group of related malformations or features

-implies genetic cause (usually)

Association

-group of malformations that appear together in recognizable pattern (more often than by chance) but w/o identified genetic cause

-ex: VACTERL

Sequence

Pattern of features caused by one primary malformation that leads to others

Field Defect

Malformations that occur together (spatially connected or embryologically connected)

Arteriovenous Malformations (AVM)

-capillaries do not form correctly/or do not form → artery connects directly to vein and pressure difference can cause it to burst

Hereditary Hemorrhagic Telangiectasia (HHT)

-AD -recurrent nosebleeds, small surface red spots (T), AVMs w/ complications from ruptures

Holoprosencephaly (HPE)

-failure of separation of the prosencephalon (forebrain) into 2 separate sides (lobes) - can be partial or complete

-assoc. with midline facial defects / often isolated

-can be caused by SHH

Dandy Walker Malformation

-abnormal cerebellum (important for coordination) -may have ID and seizures as well -cyst and abnormal or absent corpus callopsm may be present

Absence of Corpus Callosum

-Large bundle of nerves that connect two hemispheres (communication between)

-Variable (severe symptoms such as epilepsy and learning disabilities or none)

Ventriculomegaly / Hydrocephaly

-enlarges ventricles due to excess CSF

-pressure on tissue leading to brain matter loss

-assoc. w/ seizures, headaches, macrocephaly, ID, and muscle spasticity

L1 syndrome

-x-linked (L1CAM)

-Spectrum (mild to severe), adducted thumbs, ID, aqueductal stenosis → Hydrocephaly

Microcephaly

-small brain → small head

-caused by alcohol exposure, lack of 02, and/or genetics

-Primary (nonsyndromic) can be caused by genes involved in cell division

Heterotopia

-Neural migration disorder in which clumps of grey matter are abnormally placed in brain

-brain dysplasia

-can lead to seizures, DD and ID

Lissencephaly

-lack of folding (gyrations) in brain -can cause large ventricles and small head -assoc. w/ ID

Miller Dieker Lissencephaly

-17p13.3 microdel / LIS1

-ID, visual impairment, hypotonia, epilepsy, microcephaly

Schinzencephaly

-large clefts in cerebral hemispheres (loss of brain tissue)

-not generally detectable on early ultrasounds

Neural Tube Defects

-Incomplete closure of neural tube (4wk)

-multifactorial /can be caused by lack of folic acid / embryotic folding?

Spina Bifida

-spine or spinal cord not formed correctly

-varies in severity (most severe can have spinal cord herniated though back and open to air) / can be assoc. w/ movement, bladder issues, and hydrocephalus

Encephalocele

-incomplete closure of skull → brain herniating through gap (brain covered by membrane)

-those in front don't tend to contain brain tissue and fare better / outcomes depend on size and placement

Anencephaly

-failure for skull to form (brain my fail to develop it degenerate as exposed to amniotic fluid)

-born w/o forebrain or cerebellum (typically lethal)

Craniorachiachsis

-anencephaly with contiguous bonus defect → opening of spine (may be cervical or all the way down) / incredibly severe and lethal