Cilia/HYDIN
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Projects Summary Many neurological disease processes involve transient or permanent abnormalities of cerebrospinal fluid (CSF) circulation and absorption. Often, these conditions lead to increased intracranial pressure with excessive fluid accumulation, causing hydrocephalus. Cilia are organelles in various organ systems with primary established roles for fluid movement; recently associated with normal development and multiple disease processes. Ependymal cilia (lining the cerebral ventricles) are uniquely situated to play a role of blood-brain-barrier establishment, and movement of these fine hair-like structures is crucial to maintaining proper CSF flow and circulation. The identification of ciliary proteins in neurogenesis has revolutionized the pathogenesis of some diseases including hydrocephalus, retinitis pigmentosa, Bardet-Biedl syndrome (BBS) and polycystic kidney (PKD) diseases. Novel insights into the ciliary transport processes can lead to improved understanding of CSF homeostasis. HYDIN and testis specific gene (TSGA10) with their interacting partners, are ideal candidates to investigate ciliary transport pathways because of their association with hydrocephalus. Understanding these interactions leading to increased intracranial pressure will greatly advance treatment paradigms for such disorders. We hypothesize that defective spinal fluid transport and absorption is related to altered expressions of HYDIN and TSGA10 proteins. We propose to evaluate the expression levels of HYDIN and TSGA10 proteins in the hydrocephalic condition, and their interaction with other commonly known ciliary proteins. We use the hy3 mouse and HTx rat models of hydrocephalus to understand early neural function of these ciliary proteins. We expect to identify novel ciliary disease proteins and candidate genes that interact with HYDIN and TSGA10, possibly involved with CSF homeostasis and circulation in the mammalian brain.
Babak Behnam, MD, PhD
Oshio et al., 2005 |
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