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Negative regulators of the let-23 EGF receptor in Caenorhabditis elegans vulval differentiation


Jongeward, Gregg D. (1993) Negative regulators of the let-23 EGF receptor in Caenorhabditis elegans vulval differentiation. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/87ea-tr80.


Vulval induction in C. elegans is an example of the use of an EGF (Epidermal Growth Factor) mediated signal transduction system. At least five genes are involved in the negative regulation of vulval induction.

Mutations at the silent locus sli-1 (suppressor of lineage defect) are sufficient to suppress all of the phenotypes associated with hypomorphic alleles of let-23. sli-1 functions to modify the activity of let-23 but muations at sli-1 do not bypass the requirement for let-23. Based on the phenotypes of animals bearing mutations at sli-1 and other genes, sli-1 may function at or near the let-23 or sem-5 step of vulval differentiation.

Null alleles of the pleiotropic locus unc-101 cause a number of mutant phenotypes including neural defects and suppression of the vulval defects associated with some weak let-23 mutations. These unc-101 mutations interact with mutations in other genes required for proper vulval differentiation but do not act as generalized suppressors. This locus has been cloned and encodes the C. elegans homolog of the Golgi-associated clathrin adaptor protein AP47.

Animals mutant for both unc-101 and sli-1 display excessive vulval differentiation. Animals mutant at only one of these loci display no vulval abnormalities. This excessive vulval differentiation requires the inductive signal and functionallet-23, suggesting that sli-1 and unc-101 function to negatively regulate the response to the inductive signal, rather than the basal activity of let-23.

Rare mutant alleles at lin-2, lin-7, and let-23 result in excessive vulval differentiation. These alleles are genetically similar to more common alleles of these genes which result in the failure to differentiate vulval tissue. These three genes apparently are required for the activation of both positive and negative regulators of vulval differentiation.

A number of negative regulators function to control the activity of let-23. At least three pathaways of negative regulation have been genetically identified. These negative regulators act to limit the response to a growth or differentiation factor.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Biology
Degree Grantor:California Institute of Technology
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Sternberg, Paul W.
Thesis Committee:
  • Lipshitz, Howard D.
  • Lewis, Edward B.
  • Anderson, David J.
  • Emr, Scott D.
Defense Date:10 May 1993
Record Number:CaltechTHESIS:12132012-153519784
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7334
Deposited On:14 Dec 2012 16:26
Last Modified:09 Nov 2022 19:20

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