beta-Amyloid precursor protein-b is essential for Mauthner cell development in the zebrafish in a Notch-dependent manner

• Amyloid precursor protein (APP) is a transmembrane glycoprotein that has been the subject of intense research because of its implication in Alzheimer's disease. However, the physiological function of APP in the development and maintenance of the central nervous system remains largely unknown. We have previously shown that the APP homologue in zebrafish (Danio rerio), Appb, is required for motor neuron patterning and formation. Here we study the function of Appb during neurogenesis in the zebrafish hindbrain. Partial knockdown of Appb using antisense morpholino oligonucleotides blocked the formation of the Mauthner neurons, uni- or bilaterally, with an aberrant behavior as a consequence of this cellular change. The Appb morphants had decreased neurogenesis, increased notch signaling and notch] a expression at the expense of deltaA/D expression. The Mauthner cell development could be restored either by a general decrease in Notch signaling through gamma-secretase inhibition or by a partial knock down of Notch1a. Together, this demonstrates the importance of Appb in neurogenesis and for the first time shows the essential requirement of Appb in the formation of a specific cell type, the Mauthner cell, in the hindbrain during development. Our results suggest that Appb-regulated neurogenesis is mediated through balancing the Notch1a signaling pathway and provide new insights into the development of the Mauthner cell.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

APP function

Mauthner cell

Development

Zebrafish

Hindbrain

neural stem/progenitor cells

green fluorescent protein

app

intracellular domain

alzheimers-disease

lateral inhibition

gamma-secretase

controls proliferation

embryonic-development

neurogenic phenotype

genomic organization

Developmental Biology

Publikations- och innehållstyp

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