5-350 Lecture Notes - Teratology, Nevoid Basal-Cell Carcinoma Syndrome, Pitx2

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Spatial Patterning in Vertebrates
HOX CODE – Anterior/Posterior Patterning
Drosophila and Mammalian HOX Gene Clusters
Expression is sensitive to retinoic acid (anterior end of cluster is more
sensitive and therefore more easily activated by RA)
1. 4 clusters in mammals, 1 in flies
2. expressed in overlapping domains ALONG the A/P axis
3. loss of function homeotic/anterior transformation
4. gain of function posterior transformation
Hindbrain: discrete HOX gene expression boundaries along borders of
RHOMBOMERES
Hensen’s Node: secretes RA
Increases RA secretion as it moves anterior posterior
**this activates the posterior genes appropriately**
SHH INDUCTION – Dorsal/Ventral Patterning
Neural Patterning:
Notochord expresses shh neural tube floorplate induced
Later begins expressing shh
(high levels of shh induce floor plate, low levels: motor neurons)
Shh induces ventral neuronal cell types based on conc. GRADIENT
Somite Patterning:
Neural tube floorplate releases shh
Neural tube roofplate releases WNT-1
Ectodermal BMP4/7 induces roofplate and wnt expression
**Shh and Wnt act in opposition to influence ventral and dorsal
patterns, respectively**
RA sensitivity
Hindbrian
Rhombomeres
Hensen’s Node
Shh
Wnt-1
BMP 4/7
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