Specification and Function of Developmental Programmed Cell Death

Date of Award

Spring 2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Genetics

First Advisor

Hammarlund, Marc

Abstract

Programmed cell death is a crucial process for animal development. Within the developing nervous system neurons are removed through developmental programmed cell death (dPCD), altering neuronal architecture. In the central nervous system (CNS) where dPCD is controlled intrinsically, it is not clear how or why these particular cells are choosing to die since the decision is independent of their context within the nervous system. A similar intrinsically regulated dPCD is found in C. elegans. These cell deaths occur across the lineage and are highly stereotyped, so that the same 131 cells are removed in each individual. We have developed a transcriptional reporter system for interrogating the regulation of dPCD to determine how cells are deciding to die. dPCD can be prevented through null mutations in in pro-apoptotic genes, which allows us to probe the function of dPCD by observing the results of its prevention. My thesis work finds that one function of dPCD in the C. elegans nervous system is to remove variability. Normally an asymmetric cell division will produce one larger cell that survives and has a robust fate and one smaller cell that lacks a robust differentiation program and will die. When dPCD is prevented, the cells that would be removed are found to not follow the strict fate adoption that the other somatic cells have. Developmental programmed cell death is also needed for maintaining stereotyped behavior, as the presence of undead cells alters synaptic patterning and alters reversal behavior.

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