The Role of Kitlb on Development of Coordinated Muscular Contractions in the Zebrafish Gastrointestinal Tract

Abstract

Gastrointestinal (GI) motility is the spontaneous rhythmic contractions of smooth muscles that mix and propel the contents of the GI tract. Regulation of the complex muscular contractions is controlled by smooth muscles, interstitial cells of the Cajal (ICC) and enteric neurons. ICC act as pacemaker cells in the GI tract and set the frequency of spontaneous contractions. Altering ICC density results in uncoordinated GI muscular contractions. Our lab examines the role of ICC in GI motility and is focused on mechanisms that regulate ICC growth and development. Expression of the Kit receptor tyrosine kinase is used to identify ICC. Kit is stimulated by Kit ligand and stimulation is necessary for the growth and development of ICC. This project specifically examines the role of Kit – Kit ligand signaling on ICC development using the zebrafish model system. The zebrafish has two Kit genes (kita and kith) that are orthologous to human KIT, and two Kit Ligand genes (kit/a and kitlh ). I will examine the role of kitlh on the development and maturation of ICC using morpholino oligonucleotides knockdown in zebrafish. Gene expression was quantified using reverse transcriptase PCR analysis. Digital imaging techniques was used to examine morphology of the GI tract. It is anticipated that continued stimulation of kith by kitlh is necessary for development of the ICC network, and maintenance of the ICC network in adult animals.