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Publication Date

2024-5

First Advisor

Michael J. F. Barresi

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Neuroscience

Keywords

neuroscience, development, embryogenesis, zebrafish, calcium, bioelectrics, neural crest

Abstract

Alongside gene expression patterns and morphogen gradients, bioelectric patterning is potentially a key driver of development. Bioelectric patterns are characterized by fluctuations in the membrane potentials of non-excitable cells. When ionic regulators of bioelectric patterning are disrupted, developmental malformations may occur. Timothy Syndrome (TS) is a human autosomal dominant disease caused by a mutation in the cacna1c gene. cacna1c encodes the ɑ1c subunit of the L-type voltage-gated calcium (Ca2+) channel Cav1.2, which is the most commonly-occuring Ca2+ channel in the body. TS-causing mutations in the human cacna1c gene result in dysregulated Ca2+ flow through the Cav1.2 channel, such that Ca2+ moves freely across the cell membrane. TS is characterized by malformed craniofacial features, including the mandible, which is a structure derived from a population of multipotent progenitors called cranial neural crest cells (NCCs). The mechanism by which Ca2+ dysregulation in Cav1.2 channels is impacting NCC behavior during development is unknown. The role that NCCs play in establishing the craniofacial structures of the tractable model system of zebrafish is well established, therefore cacna1c expression during zebrafish embryogenesis has been characterized. Significant co-localization of cacna1c with markers for NCCs has been observed. Moreover, knockdown of cacna1c in wildtype, Marina GEVI transgenic, and Tg(sox10:nls-eos) transgenic embryos with two splice-blocking morpholinos has demonstrated broad physiological defects including but not limited to somite compaction and neural tube malformation. It may be postulated that cacna1c is an essential regulator of NCC behavior, which will shed further light on the broad importance of bioelectric patterning during embryonic development.

Rights

©2024 Mercer Kriese. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.

Language

English

Comments

122 pages: color illustrations. Includes bibliographical references (pages 83-98).

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