Diverse roles of Lef1 in the development of thalamus, pretectum and optic tectum

• Autorzy: Brozko N. , Krolak M. , Nagalski A. , MacDonald R. , Wisniewska M.B.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Lef1 is an effector of the canonical Wnt pathway that has been implicated in brain development at many stages. Lef1 is expressed specifically in the dorsal diencephalon and mesencephalon from the early stages onwards in many vertebrates. However, its role in the development of these brain parts has not been investigated so far. AIM(S): I used zebrafish as a model organism to examine the role of the widely expressed Lef1 in regulating the specification of neurons in distinct domains in the diencephalon and mesencephalon. METHOD(S): Firstly, I analyzed the spatiotemporal expression patterns of Lef1 proteins in zebrafish brain cryosections. Then I performed knockdowns of lef1 using Morpholinos, and analyzed the expression of markers that are specific for diverse progenitors (at stage 30hpf) and neurons (at stage 3dpf) in the brain. To this end I used fluorescent in situ hybridization (ISH) and visualized the larvae under confocal microscopy. RESULTS: Immunostaining revealed a strong expression of the Lef1 protein in the brain at 2dpf. ISH at the stage of progenitor domains (shh, dbx1a) showed that lef1 is not involved in their formation in diencephalon (thalamus – Th, pretectum – Pt) and mesencephalon (optic tectum – TeO). However, I observed serious impairments in expression of ascl1a and neurog1, genes characteristic for different classes of prospective neurons in the primordium of the Th, Pt and TeO. Because ascl1 is expressed in GABAergic progenitors, I hypothesized that Lef1 is involved in the specification of GABAergic neurons. I verified it at the stage of 3dpf and observed an expansion of the tcf7l2 expression that is a marker of the caudal Th, into the GABAergic rostral Th (nkx2.2a). Moreover I noted a depletion of GABAergic neurons in Pt and TeO. CONCLUSIONS: Concluding, my results implicate Lef1 in establishing the boundaries of the caudal part of Th and in the generation of GABAergic neurons in Pt and TeO. The mechanisms by which Lef1 participates in these events are yet to be understood. FINANCIAL SUPPORT: PRELUDIUM – 2013/09/N/ NZ3/01377, OPUS – 2015/19/B/NZ3/02949.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.87

Twórcy

autor

Brozko N.

• Laboratory of Molecular Neurobiology, Centre of New Technologies, University of Warsaw, Poland
• The Postgraduate School of Molecular Medicine, Medical University of Warsaw, Poland

autor

Krolak M.

• Laboratory of Molecular Neurobiology, Centre of New Technologies, University of Warsaw, Poland
• Faculty of Biology, Department of Animal Physiology, University of Warsaw, Poland

autor

Nagalski A.

• Laboratory of Molecular Neurobiology, Centre of New Technologies, University of Warsaw, Poland

autor

MacDonald R.

• Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK

autor

Wisniewska M.B.

• Laboratory of Molecular Neurobiology, Centre of New Technologies, University of Warsaw, Poland