The zinc-finger of the cerebellum 2a gene controls patterning of the anterior central nervous system during vertebrate embryogenesis. Nicholas Adam Sanek

ISBN: 9781109047295

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168 pages


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The zinc-finger of the cerebellum 2a gene controls patterning of the anterior central nervous system during vertebrate embryogenesis.  by  Nicholas Adam Sanek

The zinc-finger of the cerebellum 2a gene controls patterning of the anterior central nervous system during vertebrate embryogenesis. by Nicholas Adam Sanek
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The brain is involved in controlling myriad aspects of the daily lives of all animals. The brains of vertebrate animals are especially complex and are capable of functions as diverse as memory, emotion, reason, and consciousness. In humans, abnormalMoreThe brain is involved in controlling myriad aspects of the daily lives of all animals. The brains of vertebrate animals are especially complex and are capable of functions as diverse as memory, emotion, reason, and consciousness.

In humans, abnormal brain development can lead to devastating defects ranging from embryonic lethality, to mental retardation and paralysis. Understanding how the vertebrate brain develops is an overarching goal for many developmental neurobiologists. In my doctoral work, I have utilized the zebrafish ( Danio rerio) as a model organism to investigate how the early brain is patterned. I have chosen to focus my studies specifically on how one specific gene, zic2, controls patterning in the embryonic forebrain.

ZIC2 mutations in humans cause holoprosencephaly, a severe congenital malformation of the forebrain. Despite this observation, relatively little has been discovered about how ZIC2 controls forebrain development.-Zic2 is a transcription factor expressed throughout the dorsal central nervous system.

The DNA binding domain of Zic2 contains 5 zinc-fingers, and closely resembles the DNA binding domain of Gli transcription factors, downstream effectors of the Hedgehog (Hh) signaling pathway. In zebrafish, I have knocked-down levels of Zic2 to ask what effects on forebrain development can be attributed to Zic2 function. I discovered that one region of the diencephalon, the prethalamus, requires Zic2 function very early. Hedgehog signaling also promotes development of the prethalamus, but not till later stages of development. Zic2 depleted zebrafish also exhibit significant patterning defects in the developing optic stalks (OS) and retina.

My experiments suggest that Zic2 actually controls OS/retinal patterning through modulation of the Hh signaling pathway.-Results from my work have helped me to draw many novel conclusions regarding the mechanisms controlling patterning in the embryonic vertebrate forebrain. Insights from my work should aid in better understanding how human brains form, and hopefully provide useful information regarding the etiology of HPE in humans with ZIC2 mutations.



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