Can temperament—the set of emotional and behavioral tendencies that distinguish us from the cradle—have its roots in the earliest events of embryonic life? Temperament, understood as the biological basis of individual differences in emotional reactivity, self-regulation, and behavioral patterns [1] [2] , has historically been studied from psychological and neurobiological perspectives. Classical models, such as dimensional approaches to “activity”, “rhythmicity”, and “sensory threshold” [2] and temperament-based personality theories [3] , have emphasized genetic and postnatal maturational components [1] [4] .

However, recent advances in developmental biology and epigenetics raise the intriguing possibility that the origins of temperament may trace back to early embryonic stages, specifically to key morphogenetic processes during gastrulation, where the Spemann-Mangold organizer [5] - [7] and the notochord [8] [9] lay the structural foundations of the central nervous system (CNS). It is important to note, however, that much of the current evidence supporting these embryological influences derives from animal models and indirect human data [10] . Direct mechanistic links between these early developmental processes and specific temperamental traits in humans remain to be fully established.

This integrative perspective is crucial for three fundamental reasons:

1) Embryology-Affective Neuroscience Link: The notochord not only organizes the neural axis but also secretes molecules (e.g., Shh) that regulate brain nuclei involved in emotional regulation [11] - [13] . While animal studies provide compelling insights, human extrapolation requires validation [8] [10] .

2) Temperamental Plasticity: Epigenetic mechanisms (e.g., DNA methylation) allow in utero environmental factors (e.g., maternal stress) to modify gene expression, potentially “programming” behavioral predispositions [14] [15] . Yet, precise pathways and long-term impacts on human temperament are not fully understood [4] .

3) Clinical Implications: Alterations in early morphogenesis (e.g., notochord defects) are associated with neurodevelopmental disorders (ASD, ADHD), where temperament is an early marker [16] - [18] . Nevertheless, causality remains to be clarified [19] [20] .

While this review emphasizes embryological and early neurodevelopmental influences, alternative models highlight postnatal neural plasticity (e.g., synaptic pruning) and sociocultural factors [4] [19] [21] . These perspectives underscore lifelong biology-environment interactions. Several proposed connections remain hypothetical, supported primarily by preclinical or correlational evidence [9] [10] [16] . Further longitudinal human studies are needed to bridge embryological events and temperamental traits [18] [22] .

This narrative review aims to:

1) Synthesize evidence on the role of the Spemann-Mangold organizer and notochord in temperament ontogenesis [5] [8] - [10] ;

2) Analyze how epigenetic mechanisms mediate gene-environment modulation of temperament [14] [15] [23] ;

3) Propose an integrative model connecting embryology, neurobiology, and psychology [1] [22] [24] .

How do early morphogenetic processes (gastrulation, notochord) and epigenetic factors contribute to temperament formation, and what are the implications for individual differences and neurodevelopmental disorders?

Unlike systematic reviews, this format allows:

This narrative review was designed to critically integrate and contextualize multidisciplinary evidence on the ontogenesis of temperament, drawing from embryological, neurobiological, epigenetic, and environmental perspectives. The methodological process comprises the following stages.

This review synthesizes a provocative hypothesis: that temperament—a core construct in developmental psychology—may originate in the earliest morphogenetic events of embryonic life. The Spemann-Mangold organizer [5] - [7] and notochord [8] [9] establish molecular gradients (BMP, Wnt, Shh) that orchestrate neural tube formation and later influence circuits governing emotional reactivity and self-regulation [11] - [13] . While classical models attribute temperament to genetic and postnatal factors [1] [3] [4] , we propose that embryology provides an additional foundational layer, where disruptions in gastrulation (e.g., altered Shh signaling) may predispose to neurodevelopmental divergence [10] [16] .

However, this framework faces significant epistemological boundaries. Human evidence remains indirect, relying largely on:

Critically, while animal data show that notochord-derived Shh directs serotonergic neuron differentiation [9] [12] —a pathway implicated in emotional traits—direct causal links to human temperament are unproven.

The interplay with postnatal plasticity further complicates this model. Parenting practices [19] , cultural norms [21] , and neural rewiring throughout childhood can amplify or mitigate embryological predispositions. For example:

Four key insights emerge:

1) Embryology sets boundaries, not destiny: Early signaling establishes neural architecture, but experience-dependent plasticity continually refines temperament [4] [19] .

2) Epigenetics bridges nature and nurture: In utero environments (e.g., pollution, stress) “program” gene expression [14] [15] , yet these marks interact dynamically with postnatal experiences.

3) Clinical translation requires caution: While notochord defects predict neurodevelopmental disorders [8] [16] , biomarkers (e.g., Shh pathway genes) lack specificity for temperamental outcomes [18] .

4) Human research gaps dominate: Prospective studies tracking gastrulation-to-temperament pathways—using advanced imaging or in vitro embryoid models [10] [23] —are urgently needed.

In summary, the ontogenesis of temperament appears to be a dynamic, multilayered process involving embryological, neurobiological, epigenetic, and environmental mechanisms. While the early origins of temperament are increasingly recognized, the field must balance exciting conceptual advances with critical reflection on current empirical gaps. Bridging basic developmental science with clinical practice will require ongoing interdisciplinary collaboration and methodological innovation.