Abstract
BackgroundMembers of the vertebrate Numb family of cell fate determinants serve multiple functions throughout early embryogenesis, including an essential role in the development of the nervous system. The Numb proteins interact with various partner proteins and correspondingly participate in multiple cellular activities, including inhibition of the Notch pathway.ResultsHere, we describe the expression characteristics of Numb and Numblike (NumbL) during Xenopus development and characterize the function of NumbL during primary neurogenesis. NumbL, in contrast to Numb, is expressed in the territories of primary neurogenesis and is positively regulated by the Neurogenin family of proneural transcription factors. Knockdown of NumbL afforded a complete loss of primary neurons and did not lead to an increase in Notch signaling in the open neural plate. Furthermore, we provide evidence that interaction of NumbL with the AP-2 complex is required for NumbL function during primary neurogenesis.ConclusionWe demonstrate an essential role of NumbL during Xenopus primary neurogenesis and provide evidence for a Notch-independent function of NumbL in this context.
Highlights
Members of the vertebrate Numb family of cell fate determinants serve multiple functions throughout early embryogenesis, including an essential role in the development of the nervous system
NumbL is expressed in the areas of primary neurogenesis Mammalian Numb and NumbL have been shown to play essential roles during early development, in the context of the nervous system [12]
Loss of function studies demonstrate X. laevis NumbL is required for the differentiation of primary neurons born at the open neural plate stage
Summary
Members of the vertebrate Numb family of cell fate determinants serve multiple functions throughout early embryogenesis, including an essential role in the development of the nervous system. Numb was first identified as a membrane-associated protein that is asymmetrically segregated to only one daughter of the Drosophila sensory organ precursor cells (SOP) in the peripheral nervous system [5,6]. In this context, Numb functions as an intrinsic cell fate determinant and the daughter cell that inherits Numb adopts a different cell fate from the other daughter cell [6]. Numb is broadly expressed throughout the developing mouse and chick embryos, NumbL is highly enriched in the developing central nervous system [10,11,15]
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