Development and Pattern Formation Flashcards
central problems of developmental biology
cell fate specification
pattern formation
patternf formation
the organization of embryonic cells into a 3-dimensional body plan
What initiates pattern formation?
the establishment of axes
expression of different genes along an axis
expression of a single gene in a concentration gradient along an axis
primary patterning
establishes the body axes
secondary patterning
establishes regional or organ specific axes
At what point in development does patterning take place in humans?
mainly during weeks 4-8 of embryonic development
trhee functional classes of genes regulating fly development
1) maternal-effect genes
2) segmentation genes
3) homeotic genes
three types of segmentation genes in fly development
1) gap genes
2) pair rule genes
3) segment polarity genes
maternal effect genes
express in the drosophila egg before fertilization
gap segmentation genes
divide the embryo into broad bands
pair rule genes
further divide the embryo
segment polarity genes
divide the embryo into the final segments that are present in the adult animals
homeotic genes
genes that determine the fate or identity of body segments during development
HOX genes
first homeotic genes identified in Drosophila
all HOX genes contain a 183 bp motif called the “homeobox”
encode proteins containing a 51 amino acid binding motif called the “homeodomain”
function as transcription factors
vertebrate HOX genes
organized into 4 different complexes (A-D) on 4 different chromosomes
reason for multiple complexes is unclear, may be that developmental events are more complex and redundancy ensures normal development
How does the location of a HOX gene in the complex correlate to its expression pattern?
genes closer to the 3’ end of the complex have expression patterns that are further anterior to the embryo
two types of colinearity
temporal colinearity
spatial colinearity
spatial colinearity
the order of genes in a cluster/complex maps an axis in the developing embryo
temporal colinearity
the order of genes reflects their temporal expression during development
HOX A1 knockout
delayed closure of neural tuve in the hindbrain region, absence of several cranial nerve motor nuclei and sensory ganglia, inner ear defects and basal skull anomalies
HOX A3 kockout
craniofacial, thyroid, thymic, and cardiac anomalies
HOX B4 knockout
second cervical vertebra, the axis, transformed into a duplicate first cervical vertebra, the atlas
posterior dominance of HOX genes
when more than one HOX gene is expressed in a given segment, the HOX gene whose epxression pattern ends more posterior defines the phenotype of that segment
HOX D4 Ectopic anterior expression
occipital bones transformed into “cervical” vertebrae
rules governing HOX gene expression and function in mammals
temporal and spatial colinear expression
more HOX genes are expressed in posterior regions
if two HOX genes have overlapping expression patterns, the HOX gene whose expression ends further posterior will be dominant over the HOX gene whose expression pattern extends more anterior
considerable redundancy in function has been demonstrated between paralogous groups of HOX genes
HOX genes demonstrate colinear expression along the anterior-posterior axis of the mbryo as well as along other embryonic axes, including the limbs, GI tract, and female GU tract
mutation of human HOX D13
causes synpolydactyly
autosomal dominant trait with incomplete penetrance
maps to 2q, the region of the HOX D cluster
sequence analysis demonstrated expansions of a polyalanine stretch in the amino terminal region
hedgehog in Drosophila
segment polarity segmentation gene
later in development, necessary for patterning imaginal discs and the dorsal epidermis
mammalian hedgehog genes
three have been identified: sonic hedgehog, indian hedgehog, and desert hedgehog
secreted proteins from organizing center sand epithelium during development
organizing centers in the developing limb
zone of polarizing activity (ZPA)
apical ectodermal ridge (AER)
nonridge (dorsal) ectoderm
zone of polarizing activity (ZPA)
located in the proximal, posterior part of the limb bud
Shh is the signaling molecule
defines an anterior-posterior limb axis
apical ectodermal ridge (AER)
located in the distal edge of the limb bud
FGFs represent the signaling molecules
defines a proximal-distal limb axis
nonridge (dorsal) ectoderm
located on the dorsal aspect of the limb bud
Wnt-7a represents a signaling molecule
defines a dorsal-ventral limb axis
Describe hedgehog signaling in vertebrates
Hh inhibits Ptc, which leads to the activation of smoothened and GLI-1,2,3
this activates cell growth and differentiation pathways
holoprosencephaly
failure of prechordal mesenchyme migration and lack of sonic hedgehog inductive events, loss of function
causes abnormal septation of cerebral hemispheres and abnormality in the development of the ventral embryonic forebrain
What nervous system structures form due to high concentrations of Shh?
ventral floor plate and motor nuerons in the ventral neural tube
What nervous system structures differentiate from areas of the neural tube with lower concentrations of Shh?
dorsal areas of the tube differentiate into sensory ganglia/neurons
ventral-medial somite
the closest to the notochord, very high concentration of Shh, differentiates into the sclerotome
sclerotome
differentiates into vertebral bodies and ribs
dermomyotome
precursor of dermis and the body musculature
basal cell nevus syndrome
arises because of constitutive activation of Patched
leads to skull and rib abnormalities with a predisposition to cancer
