Isabel María García Guillén¹, Faustino Marín San Leandro², LUIS V. PUELLES LOPEZ², Mª Pilar Aroca Tejedor²

(1) 301077378601, 30800, España (Región de Murcia)
(2) REGIONALIZACION CEREBRAL Y GENES DEL DESARROLLO, IMIB-Arrixaca, España

The interpeduncular nucleus (IPN) is a limbic structure highly conserved among vertebrates. It is connected to medial habenula (mHb) afferents through the fasciculus retroflexus. The habenular-interpeduncular system (HIPS) is involved in several brain functions and behaviors such as learning and memory, stress and affective states (anxiety, depression, reward). The IPN is formed by various neuronal populations, part of which are identified by the expression of specific transcription factors (Otp, Otx2, Pax7 or Nkx6.1). To date, Pax7 is the most conspicuous marker of the IPN. During its development, each distinct IPN subpopulation follows independent tangential migratory pathways from their birthplace to their final destination in the nucleus. A recent study has shown that the transcription factor Otx2 is important for IPN development since Otx2 deletion leads to IPN migration defects. However, few studies have addressed the developmental mechanisms leading to the formation of this structure. In this work, we examine the role of the basal plate-expressed transcription factor Otp for IPN development.

We performed in situ hybridization (ISH) of IPN gene markers in sagittal sections of Otp knock-out (Otp-/-) versus wild-type (WT) mouse embryos in order to analyze the effects of Otp deletion upon Nkx6.1, Pax7 and Otx2 IPN populations.

Our study indicates that Otp deletion does not affect the Nkx6.1 and Otx2 neural populations of the IPN, since they are able to become specified and migrate to their respective locations within the nucleus. However, in Otp-/- mice, the alar Pax7 population disappears almost completely, with only few cells reaching the IPN locus.

According to our results, the transcription factor Otp has an important role for IPN development, since it controls the major molecularly distinct subpopulation of the IPN complex across its isthmic and rhombomere 1 portions. In Otp -/- mice, the large Pax7-positive alar population of the IPN is absent, causing a severe disruption of the migratory formation of this plurineuromeric nucleus.