Cerebrospinal fluid-contacting (CSF-c) cells containing monoamines such as dopamine (DA) and serotonin (5-HT) occur in the periventricular zones of the hypothalamic region of most vertebrates except for placental mammals. Here we compare the organization of the CSF-c cells in chicken, Xenopus, and zebrafish, by analyzing the expression of synthetic enzymes of DA and 5-HT, respectively, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), and draw an evolutionary scenario for this cell population. Due to the lack of TH immunoreactivity in this region, the hypothalamic CSF-c cells have been thought to take up DA from the ventricle instead of synthesizing it. We demonstrate that a second TH gene (TH2) is expressed in the CSF-c cells of all the three species, suggesting that these cells do indeed synthetize DA. Furthermore, we found that many CSF-c cells coexpress TH2 and TPH1 and contain both DA and 5-HT, a dual neurotransmitter phenotype hitherto undescribed in the brain of any vertebrate. The similarities of CSF-c cells in chicken, Xenopus, and zebrafish suggest that these characteristics are inherited from the common ancestor of the Osteichthyes. A significant difference between tetrapods and teleosts is that teleosts possess an additional CSF-c cell population around the posterior recess (PR) that has emerged in specific groups of Actinopterygii. Our comparative analysis reveals that the hypothalamus in mammals and teleosts has evolved in a divergent manner: placental mammals have lost the monoaminergic CSF-c cells, while teleosts have increased their relative number. K E Y W O R D S

Background Although the overall brain organization is shared in vertebrates, there are significant differences within subregions among different groups, notably between Sarcopterygii (lobe-finned fish) and Actinopterygii (ray-finned fish). Recent comparative studies focusing on the ventricular morphology have revealed a large diversity of the hypothalamus. Here, we study the development of the inferior lobe (IL), a prominent structure forming a bump on the ventral surface of the teleost brain. Based on its position, IL has been thought to be part of the hypothalamus (therefore forebrain). Results Taking advantage of genetic lineage-tracing techniques in zebrafish, we reveal that cells originating from her5 -expressing progenitors in the midbrain-hindbrain boundary (MHB) participate in the formation of a large part of the IL. 3D visualization demonstrated how IL develops in relation to the ventricular system. We found that IL is constituted by two developmental components: the periventricular zone of hypothalamic origin and the external zone of mesencephalic origin. The mesencephalic external zone grows progressively until adulthood by adding new cells throughout development. Conclusion Our results disprove a homology between the IL and the mammalian lateral hypothalamus. We suggest that the IL is likely to be involved in multimodal sensory integration rather than feeding motivation. The teleost brain is not a simpler version of the mammalian brain, and our study highlights the evolutionary plasticity of the brain which gives rise to novel structures. Electronic supplementary material The online version of this article (10.1186/s12915-019-0631-y) contains supplementary material, which is available to authorized users.

In the current model, the most anterior part of the forebrain (secondary prosencephalon) is subdivided into the telencephalon dorsally and the hypothalamus ventrally. Our recent study identified a new morphogenetic unit named the optic recess region (ORR) between the telencephalon and the hypothalamus. This modification of the forebrain regionalization based on the ventricular organization resolved some previously unexplained inconsistency about regional identification in different vertebrate groups. The ventricular-based comparison also revealed a large diversity within the subregions (notably in the hypothalamus and telencephalon) among different vertebrate groups. In tetrapods there is only one hypothalamic recess, while in teleosts there are two recesses. Most notably, the mammalian and teleost hypothalami are two extreme cases: the former has lost the cerebrospinal fluid-contacting (CSF-c) neurons, while the latter has increased them. Thus, one to one homology of hypothalamic subregions in mammals and teleosts requires careful verification. In the telencephalon, different developmental processes between Sarcopterygii (lobe-finned fish) and Actinopterygii (ray-finned fish) have already been described: the evagination and the eversion. Although pallial homology has been long discussed based on the assumption that the medial-lateral organization of the pallium in Actinopterygii is inverted from that in Sarcopterygii, recent developmental data contradict this assumption. Current models of the brain organization are largely based on a mammalian-centric point of view, but our comparative analyses shed new light on the brain organization of Osteichthyes.

Ascending visual projections similar to the mammalian thalamocortical pathway are found in a wide range of vertebrate species, but their homology is debated. To get better insights into their evolutionary origin, we examined the developmental origin of a thalamic-like sensory structure of teleosts, the preglomerular complex (PG), focusing on the visual projection neurons. Similarly to the tectofugal thalamic nuclei in amniotes, the lateral nucleus of PG receives tectal information and projects to the pallium. However, our cell lineage study in zebrafish reveals that the majority of PG cells are derived from the midbrain, unlike the amniote thalamus. We also demonstrate that the PG projection neurons develop gradually until late juvenile stages. Our data suggest that teleost PG, as a whole, is not homologous to the amniote thalamus. Thus, the thalamocortical-like projections evolved from a non-forebrain cell population, which indicates a surprising degree of variation in the vertebrate sensory systems.

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