Browsing by Subject "Postnatal development"

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    Dynamic Ciliary Localization in the Mouse Brain
    (2024-05) Brewer, Katlyn; Berbari, Nicolas F.; Mastracci, Teresa; Balakrishnan, Lata
    Primary cilia are hair-like structures found on nearly all mammalian cell types, including cells in the developing and adult brain. Cilia establish a unique signaling compartment for cells. For example, a diverse set of receptors and signaling proteins localize within cilia to regulate many physiological and developmental pathways including the Hh pathway. Defects in cilia structure, protein localization, or cilia function lead to genetic disorders called ciliopathies, which present with various clinical features including several neurodevelopmental phenotypes and hyperphagia associated obesity. Despite their dysfunction being implicated in several disease states, understanding their roles in CNS development and signaling has proven challenging. I hypothesize that dynamic changes to ciliary protein composition contributes to this challenge and may reflect unrecognized diversity of CNS cilia. The proteins ARL13B and ADCY3 are established ciliary proteins in the brain and assessing their localization is often used in the field to visualize cilia. ARL13B is a regulatory GTPase important for regulating cilia structure, protein trafficking, and Hh signaling, while ADCY3 is a ciliary adenylyl cyclase thought to be involved in ciliary GPCR singaling. Here, I examine the ciliary localization of ARL13B and ADCY3 in the perinatal and adult mouse brain by defining changes in the proportion of cilia enriched for ARL13B and ADCY3 depending on brain region and age. Furthermore, I identify distinct lengths of cilia within specific brain regions of male and female mice. As mice age, ARL13B cilia become relatively rare in many brain regions, including the hypothalamic feeding centers, while ADCY3 becomes a prominent cilia marker. It is important to understand the endogenous localization patterns of these proteins throughout development and under different physiological conditions as these common cilia markers may be more dynamic than initially expected. Understanding regional and development associated cilia signatures and physiological condition cilia dynamic changes in the CNS may reveal molecular mechanisms associated with ciliopathy clinical features such as obesity.
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    Increase in neuroexcitability of unmyelinated C-type vagal ganglion neurons during initial postnatal development of visceral afferent reflex functions
    (Wiley, 2013-12) Qian, Zhao; Liu, Dong‐Jie; Liu, Yang; Han, Li‐Min; Yuan, Mei; Li, Jun‐Nan; Xu, Bing; Lu, Xiao‐Long; Cao, Pan‐Xiang; Wang, Hao‐Yan; Pan, Xiao‐Dong; Wang, Li‐Juan; Qiao, Guo‐Fen; Li, Bai‐Yan; Biology, School of Science
    BACKGROUND: Baroreflex gain increase up closely to adult level during initial postnatal weeks, and any interruption within this period will increase the risk of cardiovascular problems in later of life span. We hypothesize that this short period after birth might be critical for postnatal development of vagal ganglion neurons (VGNs). METHODS: To evaluate neuroexcitability evidenced by discharge profiles and coordinate changes, ion currents were collected from identified A- and C-type VGNs at different developmental stages using whole-cell patch clamping. RESULTS: C-type VGNs underwent significant age-dependent transition from single action potential (AP) to repetitive discharge. The coordinate changes between TTX-S and TTX-R Na(+) currents were also confirmed and well simulated by computer modeling. Although 4-AP or iberiotoxin age dependently increased firing frequency, AP duration was prolonged in an opposite fashion, which paralleled well with postnatal changes in 4-AP- and iberiotoxin-sensitive K(+) current activity, whereas less developmental changes were verified in A-types. CONCLUSION: These data demonstrate for the first time that the neuroexcitability of C-type VGNs increases significantly compared with A-types within initial postnatal weeks evidenced by AP discharge profiles and coordinate ion channel changes, which explain, at least in part, that initial postnatal weeks may be crucial for ontogenesis in visceral afferent reflex function.