Abnormal hypothalamic oxytocin system in fibroblast growth factor 8-deficient mice
- PDF / 564,578 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 80 Downloads / 148 Views
ORIGINAL ARTICLE
Abnormal hypothalamic oxytocin system in fibroblast growth factor 8-deficient mice Leah R. Brooks • Wilson C. J. Chung Pei-San Tsai
•
Received: 25 March 2010 / Accepted: 28 June 2010 / Published online: 10 July 2010 Ó Springer Science+Business Media, LLC 2010
Abstract Oxytocin (OT) is a nonapeptide essential for maternal care. The development of the OT neuroendocrine system is a multi-step process dependent on the action of many transcription factors, but upstream signaling molecules regulating this process are still poorly understood. In this study, we examined if fibroblast growth factor 8 (FGF8), a signaling molecule critical for forebrain development, is essential for the proper formation of the OT system. Using immunohistochemistry, we showed a significant reduction in the number of neurons immunoreactive for the mature OT peptide in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) in the hypothalamus of homozygous (HOMO) FGF8 hypomorphic mice compared to wild-type mice. The number of neurons positive for oxyphysin prohormone in the SON but not the PVN was also significantly reduced in FGF8 HOMO hypomorphs. However, steady-state mRNA levels of the oxyphysin prohormone were not significantly different between FGF8 hypomorphs and WT mice. These data suggest that a global reduction in FGF8 signaling leads to an overall reduction of mature OT and oxyphysin prohormone levels that may have resulted from defects in multiple stages of the hormone-synthesis pathway. Since proper hormone synthesis is a hallmark of mature OT neurons, this study suggests that FGF8 signaling may contribute to the phenotypic maturation of a neuroendocrine system that originates within the diencephalon.
L. R. Brooks (&) W. C. J. Chung P.-S. Tsai Department of Integrative Physiology and the Center for Neuroscience, University of Colorado, Boulder, CO 80309-0354, USA e-mail: [email protected]
Keywords Fibroblast growth factors (FGF) FGF8 Oxytocin Oxyphysin Neurophysin Development
Introduction One of the most well-characterized endocrine functions of the oxytocin (OT) system is to stimulate mammary myoepithelial contraction, which leads to milk letdown. OT-knockout mice produce milk but cannot nurse their pups, demonstrating a critical role of this neurohormone in maternal care [1]. OT acting within the brain has also been implicated in the onset of maternal behaviors such as nesting, sniffing and exploration of pups, pup retrieval, licking, and grooming [2]. Defects in the formation or maturation of this system could lead to disruption of behaviors critical for offspring survival. OT neuron development involves a number of steps. Magnocellular neuroendocrine OT neurons are derived from the neuroepithelium lining the third ventricle by embryonic day 10.5 (E10.5). OT neurons then migrate either laterally to form the paraventricular nucleus (PVN) or ventro-laterally to form the supraoptic nucleus (SON) in the hypothalamus (HYPO) from E10.5 to E14.5 [3–5]. After migration, OT neurons target
Data Loading...
