Sagittal alignment patterns in forward head posture: an EOS-based head-to-pelvis correlation analysis.

Catecholamines (CAs) are chemical messengers with neuromodulatory and endocrine functions. Endogenous CAs include dopamine (DA), noradrenaline (NA, norepinephrine), and adrenaline (epinephrine). In addition to the roles of CAs in physiology, progressive loss of DA neurons in Parkinson’s Disease, hypodopaminergia, and altered DA signaling are some of the multiple causes behind neurodevelopmental disorders such as autism and attention deficit/hyperactivity disorder (ADHD). CA neurons can be identified by the expression of the rate-limiting enzyme Tyrosine hydroxylase (TH), which catalyzes the hydroxylation of the amino acid L-tyrosine to L-dihydroxyphenylalanine (L-DOPA; Supplementary Fig. ). Therefore, the gene has become a target for genetic manipulation of CA biosynthesis. The disruption of the locus in mice leads to mid-gestational lethality. However, surprisingly, mutant mice have been shown to still contain relevant amounts of DA in the brain and body, which has been suggested to derive from maternal bloodstream and from melanocytes. In melanocytes, the enzyme Tyrosinase (TYR) catalyzes the oxidation of tyrosine to dopaquinone, a precursor of melanin (Supplementary Fig. ). In redox reactions, dopaquinone is converted to L-DOPA, which exits melanocytes and enters the bloodstream. In wild-type (WT) mice, Tyrosinase does not make a major contribution to DA levels in the brain. However, in the absence of TH, Tyrosinase-derived L-DOPA partially substitutes NA and DA in peripheral tissues and the brain. For these reasons, genetic mammalian models have so far not been used extensively to address the developmental and behavioral consequences of CA depletion. Experimental models for DA depletion often use genetic or neurotoxin ablation of DA neurons, and pharmacological or optogenetic manipulation of DA signaling. However, these techniques do not selectively eliminate DA neuromodulation, but also non-DA functions of DA neurons, which typically have dual transmitter phenotypes, either GABAergic or glutamatergic. Further, agonist or antagonist treatments broadly act on CA receptor-expressing cells, irrespective of physiological CA signaling, and are prone to cause gain-of-function and potentially indirect effects. Despite the advances in understanding CA systems, we have limited knowledge of the role of second transmitters in DA neurons, and of the modulatory functions of DA during brain development. Therefore, we aimed at developing a genetic zebrafish model completely devoid of catecholamine transmission, but still containing the cellular complement of wild-type CA neurons.