Brain Research Bulletin 75 (2008) 231–235 Research report Conserved pattern of OTP-positive cells in the paraventricular nucleus and other hypothalamic sites of tetrapods Sylvia M. Bardet a,∗ , Margaret Martinez-de-la-Torre a , R. Glenn Northcutt b , John L.R. Rubenstein c , Luis Puelles a a Department of Human Anatomy & Psychobiology, and CIBERER Research Group 736; Medical School, University of Murcia, Murcia E30071, Spain b Department of Neuroscience, 0201 UCSD, 2310 Downwind Way, La Jolla, CA 92037, USA c Nina Ireland Laboratory of Developmental Neurobiology, Center for Neurobiology and Psychiatry, Genetics, Development and Behavioral Sciences Building, 1550 4th Street, UCSF, San Francisco, CA 94143-2611, USA Received 30 July 2007; accepted 17 October 2007 Available online 20 November 2007 Abstract The paraventricular nucleus complex (Pa) is a component of central neural circuitry that regulates several homeostatic variables. The paraven- tricular nucleus is composed of magnocellular neurons that project to the posterior pituitary and parvicellular neurons that project to numerous sites in the central nervous system. According to the revised prosomeric model, the paraventricular nucleus is located caudal to the eye stalk along the rostrocaudal dimension of the dorsal hypothalamic alar plate. Caudally, the paraventricular nucleus abuts the prethalamus (prosomere 3), and the entire complex is flanked ventrally and dorsally by Dlx5-expressing domains of the alar plate. The homeodomain transcription factor Orthopedia (Otp) is expressed in several separate hypothalamic sites: the paraventricular nucleus, perimammillary region and arcuate nucleus. In this study, we compared Otp expression in the hypothalamus of mouse (Mus musculus), chick (Gallus gallus), frog (Rana perezi) and axolotol (Ambystoma mexicanum), using immunohistochemical and in situ hybridization techniques. In all cases, Otp-positive cells in the paraventricular nucleus were excluded from Dlx5-expressing adjacent domains. Other positive neuronal populations were observed in the arcuate nucleus and oblique perimam- millary band. Expression in the medial amygdala appears to be continuous with the Otp-expressing paraventricular nucleus complex. This area is relatively unevaginated in the amphibian brains, barely evaginated in the chick, and fully evaginated in the mouse. These data led us to conclude that the expression pattern of Otp is topologically highly conserved in tetrapods and is plesiomorphic among chordates. © 2007 Elsevier Inc. All rights reserved. Keywords: Orthopedia; Dlx; Paraventricular nucleus; Medial amygdala; Forebrain Abbreviations: A, amygdala; aPO, accessory preoptic nucleus; Ar, arcuate nucleus; cp, choroid plexus; Dll, Drosophila distalless protein; Dlx, vertebrate distalless gene; PThE, prethalamic eminence; hBP, hypothalamic basal plate; Hy, hypothalamus; III, third ventricle; LHA, lateral hypothalamic area; lv, lat- eral ventricle; MeA, medial amygdala; MB, mammillary band; OB, olfactory bulb; oc, optic chiasma; ot, optic tract; OTP, orthopedia protein; P, pallium; Pa, paraventricular nucleus complex; PO, preoptic area; por, preoptic recess; PTh, prethalamus; PT, pretectum; PaC, caudal paraventricular nucleus; vPaC, cau- dal paraventricular nucleus; ventral part; dPaC, caudal paraventricular nucleus; dorsal part; PaR, rostral paraventricular nucleus; Se, septum; SPall, subpallium; SPa, subparaventricular area; T, telencephalon; Th, thalamus; zli, zona limitans intrathalamica. ∗ Corresponding author. Tel.: +34 9683 63954; fax: +34 9683 63955. E-mail address: sbardet@um.es (S.M. Bardet). 1. Introduction Developmental and comparative analysis of the paraventric- ular nucleus complex needs to consider its topological location in the hypothalamus. Evidence from various experimental data on axial mesodermal induction implies that the hypothalamus is a rostral forebrain entity, ventral to the telencephalon, not to the thalamus (see reviews in [8–11]). Thus, the Herrick–Kuhlenbeck assumption that the hypothalamus is a homogeneous longitu- dinal subdivision of the forebrain [4,5] has turned out to be inconsistent with multiple lines of evidence. The hypothalamus accordingly lies rostral to the prethalamus and the prethala- mic tegmentum (p3 prosomere of the diencephalon; old term: ventral thalamus) and is likewise composed of basal and alar parts. The mammillary and infundibular hypothalamic domains 0361-9230/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.brainresbull.2007.10.037