Study of the IRM family of cell adhesion molecules during animal development: functions, regulation and evolutionary conservation

Abstract

The Irre cell-recognition module (IRM) comprises a small group of evolutionarily conserved type I transmembrane glycoproteins belonging to the immunoglobulin superfamily, originally characterized in D. melanogaster, that act in concert and in a partially redundant manner, in a wide range of developmental processes that require cell recognition, adhesion and intercellular signaling. In humans, mutations affecting the IRM genes affect kidney and heart development and can cause cognition deficiencies. Here we propose to study the IRM function and evolution in a comprehensive and integrated way, employing two standard animal models traditionally used in developmental biology (Drosophila melanogaster and Gallus gallus).and four complementary approches, using different levels of analysis: a) Transcriptional quantification of the genes comprising the IRM family during D. melanogaster development and identification of their regulatory factors including their co-regulation aiming at a more complete definition of the genetic circuitry and protein interation networks that directly control and modulate functioning and expression of this gene family; b) To extend and refine previous structure-function analyses through "in situ" mutagenesis, using a CRISPR RNA/Cas9 system, of the genomic regions encoding the intracellular structural domains of Rst and Kirre proteins, two of the best studied Drosophila IRM components; c) Characterization of the still poorly understood functions of D. melanogaster IRM in the ovary, salivary gland and embryonic nervous system aiming at more general description of the role of this functional module in the insect embryonic and post embryonic development; d) To understand in more depth the atypical IRM family of Gallus gallus, whose characterization was recently started in our lab. (AU)