Retinoic Acid Receptor β Controls Development of Striatonigral Projection Neurons through FGF-Dependent and Meis1-Dependent Mechanisms.
The mammalian striatum controls sensorimotor and psychoaffective functions through coordinated activities of its two striatonigral and striatopallidal output pathways. Here we show that retinoic acid receptor β (RARβ) controls development of a subpopulation of GABAergic, Gad65-positive striatonigral projection neurons. In Rarb(-/-) knock-out mice, concomitant reduction of Gad65, dopamine receptor D1 (Drd1), and substance P expression at different phases of prenatal development was associated with reduced number of Drd1-positive cells at birth, in contrast to normal numbers of striatopallidal projection neurons expressing dopamine receptor D2. Fate mapping using BrdU pulse-chase experiments revealed that such deficits may originate from compromised proliferation of late-born striosomal neurons and lead to decreased number of Drd1-positive cells retaining BrdU in postnatal day (P) 0 Rarb(-/-) striatum. Reduced expression of Fgf3 in the subventricular zone of the lateral ganglionic eminence (LGE) at embryonic day 13.5 may underlie such deficits by inducing premature differentiation of neuronal progenitors, as illustrated by reduced expression of the proneural gene Ascl1 (Mash1) and increased expression of Meis1, a marker of postmitotic LGE neurons. In agreement with a critical role of FGF3 in this control, reduced number of Ascl1-expressing neural progenitors, and a concomitant increase of Meis1-expressing cells, were observed in primary cell cultures of Rarb(-/-) LGE. This defect was normalized by addition of fibroblast growth factor (FGF). Such data point to role of Meis1 in striatal development, also supported by reduced neuronal differentiation in the LGE of Meis1(-/-) embryos. Our data unveil a novel mechanism of development of striatonigral projection neurons involving retinoic acid and FGF, two signals required for positioning the boundaries of Meis1-expressing cells.
Developmental Biology and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut de la Santé et de la Recherche Médicale, U964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, Fédération de Médecine Translationnelle de Strasbourg, and Université de Strasbourg, 67404 Illkirch, France, and.
Monika
M
Rataj-Baniowska
Developmental Biology and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut de la Santé et de la Recherche Médicale, U964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, Fédération de Médecine Translationnelle de Strasbourg, and Université de Strasbourg, 67404 Illkirch, France, and.
Anna
A
Niewiadomska-Cimicka
Developmental Biology and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut de la Santé et de la Recherche Médicale, U964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, Fédération de Médecine Translationnelle de Strasbourg, and Université de Strasbourg, 67404 Illkirch, France, and.
Marie
http://orcid.org/0000-0002-9490-8997
M
Paschaki
Developmental Biology and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut de la Santé et de la Recherche Médicale, U964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, Fédération de Médecine Translationnelle de Strasbourg, and Université de Strasbourg, 67404 Illkirch, France, and.
Monika
M
Szyszka-Niagolov
Centro Nacional de Investigaciones Cardiovasculares, CNIC, Madrid 28029, Spain.
Laura
http://orcid.org/0000-0002-1661-618X
L
Carramolino
Centro Nacional de Investigaciones Cardiovasculares, CNIC, Madrid 28029, Spain.
Miguel
M
Torres
Developmental Biology and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut de la Santé et de la Recherche Médicale, U964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, Fédération de Médecine Translationnelle de Strasbourg, and Université de Strasbourg, 67404 Illkirch, France, and.
Pascal
P
Dollé
Developmental Biology and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut de la Santé et de la Recherche Médicale, U964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, Fédération de Médecine Translationnelle de Strasbourg, and Université de Strasbourg, 67404 Illkirch, France, and krezel@igbmc.fr.
Wojciech
http://orcid.org/0000-0003-1605-3185
W
Krężel
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D005260:Female; D051518:Fibroblast Growth Factor 3 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D061251:Primary Cell Culture; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology / Q000196:embryology / Q000502:physiology*
D000963:Antimetabolites; D051518:Fibroblast Growth Factor 3; D018398:Homeodomain Proteins; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D017447:Receptors, Dopamine D1; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D005346:Fibroblast Growth Factors; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D001973:Bromodeoxyuridine
FGF; MEIS1; dopamine receptors; neurogenesis; retinoic acid receptors; striatum